TW542823B - A compound having potassium channel inhibition activity potassium channel inhibitors - Google Patents
A compound having potassium channel inhibition activity potassium channel inhibitors Download PDFInfo
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- TW542823B TW542823B TW088101240A TW88101240A TW542823B TW 542823 B TW542823 B TW 542823B TW 088101240 A TW088101240 A TW 088101240A TW 88101240 A TW88101240 A TW 88101240A TW 542823 B TW542823 B TW 542823B
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- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
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- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000005429 oxyalkyl group Chemical group 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000012402 patch clamp technique Methods 0.000 description 1
- YBVNFKZSMZGRAD-UHFFFAOYSA-N pentamidine isethionate Chemical compound OCCS(O)(=O)=O.OCCS(O)(=O)=O.C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 YBVNFKZSMZGRAD-UHFFFAOYSA-N 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
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- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- TYRGSDXYMNTMML-UHFFFAOYSA-N propyl hydrogen sulfate Chemical compound CCCOS(O)(=O)=O TYRGSDXYMNTMML-UHFFFAOYSA-N 0.000 description 1
- ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical compound CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 229910052704 radon Inorganic materials 0.000 description 1
- SYUHGPGVQRZVTB-UHFFFAOYSA-N radon atom Chemical compound [Rn] SYUHGPGVQRZVTB-UHFFFAOYSA-N 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000002336 repolarization Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/20—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/28—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Magnetic Heads (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- External Artificial Organs (AREA)
- Seasonings (AREA)
- Sorption Type Refrigeration Machines (AREA)
- Plural Heterocyclic Compounds (AREA)
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| HU (1) | HUP0101269A3 (enExample) |
| ID (1) | ID25853A (enExample) |
| IL (1) | IL137219A0 (enExample) |
| NO (1) | NO20003600L (enExample) |
| NZ (1) | NZ505666A (enExample) |
| PL (1) | PL341859A1 (enExample) |
| RU (1) | RU2218330C2 (enExample) |
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| US6333349B1 (en) * | 1997-02-26 | 2001-12-25 | Aventis Pharma Deutschland Gmbh | Sulfonamide-substituted fused 7-membered ring compounds, their use as a medicament, and pharmaceutical preparations comprising them |
| EP1109544A4 (en) | 1998-09-01 | 2004-10-27 | Bristol Myers Squibb Co | POTASSIUM CHANNEL INHIBITORS AND THEIR METHOD OF USE |
| CA2385047A1 (en) * | 1999-09-22 | 2001-03-29 | Ann H. Cornell-Bell | Uses of kappa-conotoxin pviia |
| EP1240147A1 (en) * | 1999-12-21 | 2002-09-18 | Icagen, Inc. | Potassium channel inhibitors |
| US6566380B2 (en) * | 2000-07-25 | 2003-05-20 | Icagen, Inc. | Potassium channel inhibitors |
| US6620849B2 (en) | 2000-07-26 | 2003-09-16 | Icafen, Inc. | Potassium channel inhibitors |
| DE10059418A1 (de) * | 2000-11-30 | 2002-06-20 | Aventis Pharma Gmbh | Ortho, meta-substituierte Bisarylverbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10060807A1 (de) | 2000-12-07 | 2002-06-20 | Aventis Pharma Gmbh | Ortho, ortho-substituierte stickstoffhaltige Bisarylverbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10061876A1 (de) * | 2000-12-12 | 2002-06-20 | Aventis Pharma Gmbh | Arylierte Furan- und Thiophencarbonsäureamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| US6849634B2 (en) | 2000-12-21 | 2005-02-01 | Icagen | Potassium channel inhibitors |
| DE10121003A1 (de) | 2001-04-28 | 2002-12-19 | Aventis Pharma Gmbh | Anthranilsäureamide, Verfahren zur Herstellung, ihrer Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| US7470518B2 (en) | 2002-02-12 | 2008-12-30 | Cellectricon Ab | Systems and method for rapidly changing the solution environment around sensors |
| US20060078961A1 (en) | 2002-02-12 | 2006-04-13 | Daniel Chiu | Systems and methods for rapidly changing the solution environment around sensors |
| US20030199578A1 (en) * | 2002-04-19 | 2003-10-23 | Turner Sean C. | Naphthalene amides as potassium channel openers |
| BR0309940A (pt) * | 2002-05-08 | 2005-02-09 | Bayer Healthcare Ag | Derivados de hidróxi-tetraidro-naftaleniluréia |
| WO2004052846A1 (en) * | 2002-12-06 | 2004-06-24 | Bayer Healthcare Ag | Tetrahydro-naphthalene derivatives |
| US7544716B2 (en) * | 2002-12-09 | 2009-06-09 | Xention Limited | Tetrahydro-naphthalene derivatives as vanilloid receptor antagonists |
| GB0315950D0 (en) | 2003-06-11 | 2003-08-13 | Xention Discovery Ltd | Compounds |
| US7638515B2 (en) | 2003-10-08 | 2009-12-29 | Bayer Schering Pharma Aktiengesellschaft | Tetrahydronaphthalene derivatives, process for their production and their use as anti-inflammatory agents |
| SI1670458T1 (sl) | 2003-10-08 | 2007-06-30 | Bayer Schering Pharma Ag | Tetrahidronaftalenski derivati, postopek za njihovo pripravo in njihova uporaba kot antiinflamatoriki |
| US7662821B2 (en) | 2003-10-08 | 2010-02-16 | Bayer Schering Pharma Ag | Tetrahydronaphthalene derivatives, process for their production and their use as anti-inflammatory agents |
| US20080153859A1 (en) | 2004-04-05 | 2008-06-26 | Hartmut Rehwinkel | Multiply-substituted tetrahydronaphthalene derivatives, process for their production and their use as anti-inflammatory agents |
| GB0412986D0 (en) | 2004-06-10 | 2004-07-14 | Xention Discovery Ltd | Compounds |
| US7576212B2 (en) | 2004-12-09 | 2009-08-18 | Xention Limited | Thieno[2,3-B] pyridines as potassium channel inhibitors |
| DE102005017316A1 (de) * | 2005-04-14 | 2006-10-19 | Schering Ag | Tetrahydronaphthalinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Entzündungshemmer |
| GB0525164D0 (en) | 2005-12-09 | 2006-01-18 | Xention Discovery Ltd | Compounds |
| EP1834948A1 (de) | 2006-03-15 | 2007-09-19 | Bayer Schering Pharma Aktiengesellschaft | Tetrahydronaphthalinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Entzündungshemmer |
| JP2009536156A (ja) * | 2006-04-14 | 2009-10-08 | ノバルティス アクチエンゲゼルシャフト | ヘッジホッグ経路関連障害の処置におけるビアリールカルボキサミドの使用 |
| DE102006019589A1 (de) * | 2006-04-27 | 2007-10-31 | Sanofi-Aventis Deutschland Gmbh | Inhibitoren des TASK-1 und Task-3 Ionenkanals |
| ES2420960T3 (es) * | 2006-08-23 | 2013-08-28 | Valeant Pharmaceuticals International | Derivados de 4-(N-azacicloalquil)anilidas como moduladores de los canales de potasio |
| AU2007325629A1 (en) * | 2006-11-28 | 2008-06-05 | Valeant Pharmaceuticals International | 1,4 diamino bicyclic retigabine analogues as potassium channel modulators |
| GB0815784D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB0815781D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB0815782D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB201105659D0 (en) | 2011-04-01 | 2011-05-18 | Xention Ltd | Compounds |
| NO3175985T3 (enExample) | 2011-07-01 | 2018-04-28 | ||
| WO2013112932A1 (en) | 2012-01-27 | 2013-08-01 | Gilead Sciences, Inc. | Combination therapies using late sodium ion channel blockers and potassium ion channel blockers |
| EP4074696A4 (en) | 2021-10-27 | 2024-01-31 | Shanghai Zhimeng Biopharma, Inc. | POTASSIUM CHANNEL REGULATOR COMPOUND, PRODUCTION AND USE THEREOF |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3953506A (en) | 1974-02-07 | 1976-04-27 | American Cyanamid Company | Ureidotetralin compounds |
| US4005140A (en) | 1974-02-07 | 1977-01-25 | American Cyanamid Company | Ureidotetralin compounds |
| GB1479544A (en) | 1974-02-07 | 1977-07-13 | American Cyanamid Co | 1,2,3,4-tetrahydro-1-naphthylurea derivatives their preparation and their use |
| GB8707123D0 (en) | 1987-03-25 | 1987-04-29 | Pfizer Ltd | Antiarrhythmic agents |
| US5006512A (en) | 1987-10-02 | 1991-04-09 | Tsuyoshi Ohnishi | Therapeutic usages of inhibitors for a potassium efflux channel |
| IL88314A (en) | 1987-11-18 | 1994-05-30 | Tanabe Seiyaku Co | Sulphonylamino indane derivatives, their preparation and pharmaceutical compositions containing them |
| DK691488A (da) | 1987-12-14 | 1989-06-15 | Beecham Group Plc | Hidtil ukendte forbindelser |
| US5242947A (en) | 1988-02-10 | 1993-09-07 | New York University | Use of polyamines as ionic-channel regulating agents |
| DE3818245A1 (de) | 1988-05-28 | 1989-12-07 | Hoechst Ag | Kombination von angiotensin-converting-enzyme-hemmern mit kaliumkanal-modulatoren sowie deren verwendung in arzneimitteln |
| KR100195656B1 (ko) * | 1989-05-31 | 1999-06-15 | 로버트 에이.아미테이지 | 치료학적으로 유용한 2-아미노테트랄린 유도체 |
| US5215985A (en) | 1990-07-20 | 1993-06-01 | E. R. Squibb & Sons, Inc. | Method for treating ischemic insult to neurons employing an ATP-sensitive potassium channel blocker |
| ATE167473T1 (de) | 1990-08-20 | 1998-07-15 | Eisai Co Ltd | Sulfonamid-derivate |
| US5401848A (en) | 1990-11-26 | 1995-03-28 | E. R. Squibb & Sons, Inc. | Indane and quinoline derivatives |
| US5310932A (en) | 1991-04-15 | 1994-05-10 | E. R. Squibb & Sons, Inc. | Chromanyl substituted indole potassium channel openers |
| US5234947A (en) | 1991-11-07 | 1993-08-10 | New York University | Potassium channel activating compounds and methods of use thereof |
| US5356775A (en) | 1992-07-29 | 1994-10-18 | Brigham & Women's Hospital | Primary structure for functional expression from complementary DNA of a mammalian ATP-sensitive potassium channel |
| US5328830A (en) | 1992-09-08 | 1994-07-12 | Miles Inc. | Potassium channel modulators |
| US5453421A (en) | 1992-09-11 | 1995-09-26 | E. R. Squibb & Sons, Inc. | Aryl and heterocyclic substituted propenamide derivatives |
| US5374643A (en) | 1992-09-11 | 1994-12-20 | E. R. Squibb & Sons, Inc. | Aryl urea (thiourea) and cyanoguanidine derivatives |
| DE4302051A1 (de) | 1993-01-26 | 1994-07-28 | Thomae Gmbh Dr K | 5-gliedrige Heterocyclen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| GB9309716D0 (en) | 1993-05-12 | 1993-06-23 | Zeneca Ltd | Heterocyclic derivatives |
| US5401758A (en) | 1993-10-07 | 1995-03-28 | Bristol-Myers Squibb Company | Pyridinyl cyanoguanidine compounds |
| US5631275A (en) | 1993-12-30 | 1997-05-20 | Hoechst Aktiengesellschaft | Substituted benzenesulfonylureas and -thioureas, preparation processes and possible uses of pharmaceutical preparations based on these compounds |
| FR2717805B1 (fr) | 1994-03-28 | 1996-05-10 | Rhone Poulenc Rorer Sa | Dérivés de 5H-indeno[1,2-b]pyrazine-2,3-dione, leur préparation et les médicaments les contenant . |
| US5615460A (en) | 1994-06-06 | 1997-04-01 | The Procter & Gamble Company | Female component for refastenable fastening device having regions of differential extensibility |
| ZA96211B (en) | 1995-01-12 | 1996-07-26 | Teva Pharma | Compositions containing and methods of using 1- aminoindan and derivatives thereof and process for preparing optically active 1-aminoindan derivatives |
| WO1996036596A1 (en) | 1995-05-19 | 1996-11-21 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
| JP2001521484A (ja) | 1996-01-22 | 2001-11-06 | イーライ・リリー・アンド・カンパニー | 置換されたインダンのライブラリーを製造するための組み合わせ方法 |
| US6083986A (en) | 1996-07-26 | 2000-07-04 | Icagen, Inc. | Potassium channel inhibitors |
| US6048877A (en) | 1997-02-21 | 2000-04-11 | Bristol-Myers Squibb Company | Tetralone derivatives as antiarrhythmic agents |
-
1999
- 1999-01-13 US US09/229,315 patent/US6333337B1/en not_active Expired - Fee Related
- 1999-01-26 ZA ZA9900550A patent/ZA99550B/xx unknown
- 1999-01-27 IL IL13721999A patent/IL137219A0/xx unknown
- 1999-01-27 BR BR9907236-0A patent/BR9907236A/pt not_active IP Right Cessation
- 1999-01-27 TW TW088101240A patent/TW542823B/zh not_active IP Right Cessation
- 1999-01-27 ID IDW20001654A patent/ID25853A/id unknown
- 1999-01-27 AU AU22419/99A patent/AU745845B2/en not_active Ceased
- 1999-01-27 HU HU0101269A patent/HUP0101269A3/hu unknown
- 1999-01-27 JP JP2000528531A patent/JP2002501041A/ja active Pending
- 1999-01-27 EP EP99902443A patent/EP1051394B1/en not_active Expired - Lifetime
- 1999-01-27 RU RU2000122451/04A patent/RU2218330C2/ru not_active IP Right Cessation
- 1999-01-27 CN CN99804373A patent/CN1294577A/zh active Pending
- 1999-01-27 CA CA002317457A patent/CA2317457A1/en not_active Abandoned
- 1999-01-27 KR KR1020007008128A patent/KR20010034377A/ko not_active Withdrawn
- 1999-01-27 TR TR2000/02191T patent/TR200002191T2/xx unknown
- 1999-01-27 PL PL99341859A patent/PL341859A1/xx not_active Application Discontinuation
- 1999-01-27 AT AT99902443T patent/ATE265426T1/de not_active IP Right Cessation
- 1999-01-27 NZ NZ505666A patent/NZ505666A/xx unknown
- 1999-01-27 WO PCT/US1999/001663 patent/WO1999037607A1/en not_active Ceased
- 1999-01-27 DE DE69916792T patent/DE69916792D1/de not_active Expired - Lifetime
-
2000
- 2000-07-13 NO NO20003600A patent/NO20003600L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR9907236A (pt) | 2002-01-22 |
| NO20003600D0 (no) | 2000-07-13 |
| CN1294577A (zh) | 2001-05-09 |
| ID25853A (id) | 2000-11-09 |
| WO1999037607A1 (en) | 1999-07-29 |
| HUP0101269A3 (en) | 2003-01-28 |
| ZA99550B (en) | 1999-07-26 |
| NZ505666A (en) | 2002-11-26 |
| KR20010034377A (ko) | 2001-04-25 |
| CA2317457A1 (en) | 1999-07-29 |
| NO20003600L (no) | 2000-09-26 |
| US6333337B1 (en) | 2001-12-25 |
| EP1051394A1 (en) | 2000-11-15 |
| AU2241999A (en) | 1999-08-09 |
| TR200002191T2 (tr) | 2000-11-21 |
| HUP0101269A1 (hu) | 2001-10-28 |
| EP1051394B1 (en) | 2004-04-28 |
| PL341859A1 (en) | 2001-05-07 |
| RU2218330C2 (ru) | 2003-12-10 |
| AU745845B2 (en) | 2002-04-11 |
| IL137219A0 (en) | 2001-07-24 |
| JP2002501041A (ja) | 2002-01-15 |
| DE69916792D1 (de) | 2004-06-03 |
| ATE265426T1 (de) | 2004-05-15 |
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